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2. Beyond the Norm: Epidemiology of Irritable Bowel Syndrome and Mental Health Among Sexual and Gender-Diverse Young Adults in a Large Representative Cohort

Author

Voorspoels, Wouter, Proost, Sebastian, Mortier, Philippe, Kiekens, Glenn, Alonso, Jordi, Raes, Jeroen, Falony, Gwen, Vieira-Silva, Sara, van Oudenhove, Lukas, Cuijpers, Pim, Auerbach, Randy P., Bootsma, Erik, Jansen, Leontien, Van Den Houte, Karen, Kessler, Ronald C., Tack, Jan, and Bruffaerts, Ronny

Published
2024
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4. Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility

Author

Caenepeel, Clara, Deleu, Sara, Vazquez Castellanos, Jorge Francisco, Arnauts, Kaline, Braekeleire, Sara, Machiels, Kathleen, Baert, Filip, Mana, Fazia, Pouillon, Lieven, Hindryckx, Pieter, Lobaton, Triana, Louis, Edouard, Franchimont, Denis, Verstockt, Bram, Ferrante, Marc, Sabino, João, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, and Vermeire, Séverine

Published
2024
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5. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

Author

Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf

Published
2023
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6. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author

Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe-Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Zucker, Jean-Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, and Dumas, Marc-Emmanuel

Published
2023
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7. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author

Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I, Raygoza Garay, Juan Antonio, Finnicum, Casey T, Liu, Xingrong, Zhernakova, Daria V, Bonder, Marc Jan, Hansen, Tue H, Frost, Fabian, Rühlemann, Malte C, Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A, Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D, Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T, Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I, Burk, Robert D, Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E, van Duijn, Cornelia M, Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A, Ijzerman, Richard G, Jackson, Matthew A, Jaddoe, Vincent WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, Moll, Henriette A, Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J, Steves, Claire J, Thorsen, Jonathan, Timpson, Nicholas J, Tito, Raul Y, Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H, Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U, Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, Meyer, Katie A, Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C, Spector, Tim D, Uitterlinden, Andre G, Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M, Franke, Lude, Sanna, Serena, D’Amato, Mauro, and Pedersen, Oluf

Subjects
Microbiology, Biological Sciences, Genetics, Human Genome, Biotechnology, Clinical Research, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adolescent, Adult, Bifidobacterium, Child, Child, Preschool, Cohort Studies, Female, Gastrointestinal Microbiome, Genetic Variation, Genome-Wide Association Study, Humans, Lactase, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Metabolism, Quantitative Trait Loci, RNA, Ribosomal, 16S, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P

Published
2021

10. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author

Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Schmidt, Thomas S. B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean-Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc-Emmanuel, Ehrlich, S. Dusko, and Pedersen, Oluf

Published
2022
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13. RIGOROUS DONOR SELECTION FOR FMT IN ACTIVE ULCERATIVE COLITIS: KEY LESSONS FROM A RANDOMIZED CONTROLLED TRIAL HALTED FOR FUTILITY

Author

Caenepeel, Clara, primary, Deleu, Sara, additional, Vazquez Castellanos, Jorge Francisco, additional, Arnauts, Kaline, additional, Braekeleire, Sara, additional, Machiels, Kathleen, additional, Baert, Filip, additional, Mana, Fazia, additional, Pouillon, Lieven, additional, Hindryckx, Pieter, additional, Lobaton, Triana, additional, Louis, Edouard, additional, Franchimont, Denis, additional, Verstockt, Bram, additional, Ferrante, Marc, additional, Sabino, João, additional, Vieira-Silva, Sara, additional, Falony, Gwen, additional, Raes, Jeroen, additional, and Vermeire, Séverine, additional

Published
2024
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14. Combinatorial, additive and dose-dependent drug-microbiome associations

Author

Forslund, Sofia K., Chakaroun, Rima, Zimmermann-Kogadeeva, Maria, Markó, Lajos, Aron-Wisnewsky, Judith, Nielsen, Trine, Moitinho-Silva, Lucas, Schmidt, Thomas S.B., Falony, Gwen, Vieira-Silva, Sara, Adriouch, Solia, Alves, Renato J., Assmann, Karen, Bastard, Jean-Philippe, Birkner, Till, Caesar, Robert, and Chilloux, Julien

Subjects
Microbiota (Symbiotic organisms) -- Physiological aspects, Pharmacology, Experimental, Metabolic diseases -- Drug therapy, Cardiovascular diseases -- Drug therapy, Dose-response relationship (Biochemistry) -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery.sup.1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease., Author(s): Sofia K. Forslund [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] [sup.6] , Rima Chakaroun [sup.7] , Maria Zimmermann-Kogadeeva [sup.1] , Lajos Markó [sup.2] [sup.4] [sup.5] , Judith Aron-Wisnewsky [sup.8] [sup.9] , [...]

Published
2021
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15. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author

Vieira-Silva, Sara, Falony, Gwen, Belda, Eugeni, Nielsen, Trine, Aron-Wisnewsky, Judith, Chakaroun, Rima, and Forslund, Sofia K.

Subjects
Microbiota (Symbiotic organisms) -- Control -- Causes of -- Analysis, Dysbiosis -- Drug therapy -- Distribution, Statins -- Dosage and administration, Overweight persons -- Diseases -- Analysis, Prevalence studies (Epidemiology) -- Analysis, Company distribution practices, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans.sup.1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities.sup.1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease.sup.2. Reported changes in stool consistency.sup.3 and inflammation status.sup.4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs., Author(s): Sara Vieira-Silva [sup.1] [sup.2] , Gwen Falony [sup.1] [sup.2] , Eugeni Belda [sup.3] [sup.4] , Trine Nielsen [sup.5] , Judith Aron-Wisnewsky [sup.3] [sup.6] , Rima Chakaroun [sup.7] , Sofia [...]

Published
2020
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25. Fat and not sugar as the determining factor for gut microbiota changes, obesity and related metabolic disorders in mice

Author

UCL - SSS/LDRI - Louvain Drug Research Institute, Suriano, Francesco, Vieira-Silva, Sara, Falony, Gwen, de Wouters d'Oplinter, Alice, Paone, Paola, Delzenne, Nathalie M., Everard, Amandine, Raes, Jeroen, Van Hul, Matthias, Cani, Patrice D., UCL - SSS/LDRI - Louvain Drug Research Institute, Suriano, Francesco, Vieira-Silva, Sara, Falony, Gwen, de Wouters d'Oplinter, Alice, Paone, Paola, Delzenne, Nathalie M., Everard, Amandine, Raes, Jeroen, Van Hul, Matthias, and Cani, Patrice D.

Abstract

Diet-induced obesity contributes to the development of type 2 diabetes, insulin resistance, metabolic inflammation, oxidative and endoplasmic reticulum (ER) stress. Overall, obesity is associated with deviations in the composition and functionality of the gut microbiota. There are many divergent findings regarding the link between the excessive intake of certain dietary components (i.e., fat and sugar) and obesity development. We therefore investigated the effect of specific diets, with a different content in sugar and fat, in promoting obesity and related comorbidities as well as their impact on microbial load and gut microbiota composition/diversity.C57BL/6J mice were fed either a low-sugar, low-fat control diet (CT), a high-sugar diet (HS), a high-fat, high-sugar diet (HF/HS), or a high-fat diet (HF) for 8 weeks. The impact of the different diets on obesity, glucose metabolism, inflammation, and oxidative and ER stress were determined. Diet-induced changes in the gut microbiota composition and density were also analyzed.HF diet-fed mice showed the highest body weight and fat mass gains and displayed the most impaired glucose and insulin profiles. HS, HF/HS, and HF diets differently affected hepatic cholesterol content and mRNA expression of several markers associated with immune cells, inflammation, oxidative and ER stress in several organs/tissues. Additionally, HF diet feeding resulted in a decreased microbial load at the end of the experiment. When analyzing the gut microbiota composition, we found that HS, HF/HS, and HF diets induced specific changes in the abundance of certain bacterial taxa. Taken together, our results highlight that dietary intake of different macronutrients distinctively impacts the development of an obese/diabetic state and the regulation of metabolic inflammation in specific organs. We propose that these differences are not only obesity-driven but that changes in the gut microbiota composition may play a key role in this context.

Published
2023

26. Advancing human gut microbiota research by considering gut transit time

Author

Procházková, Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, Roager, Henrik Munch, Procházková, Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, and Roager, Henrik Munch

Abstract

Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet–microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.

Published
2023

27. Advancing human gut microbiota research by considering gut transit time

Author

Procházková , Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, Roager, Henrik M., Procházková , Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, and Roager, Henrik M.

Abstract

Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet–microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.

Published
2023

28. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

Author

Zhernakova, Alexandra, Kurilshikov, Alexander, Bonder, Marc Jan, Tigchelaar, Ettje F., Schirmer, Melanie, Vatanen, Tommi, Mujagic, Zlatan, Vila, Arnau Vich, Falony, Gwen, Vieira-Silva, Sara, Wang, Jun, Imhann, Floris, Brandsma, Eelke, Jankipersadsing, Soesma A., Joossens, Marie, Cenit, Maria Carmen, Deelen, Patrick, Swertz, Morris A., study, LifeLines cohort, Weersma, Rinse K., Feskens, Edith J. M., Netea, Mihai G., Gevers, Dirk, Jonkers, Daisy, Franke, Lude, Aulchenko, Yurii S., Huttenhower, Curtis, Raes, Jeroen, Hofker, Marten H., Xavier, Ramnik J., Wijmenga, Cisca, and Fu, Jingyuan

Published
2016

29. Population-level analysis of gut microbiome variation

Author

Falony, Gwen, Joossens, Marie, Vieira-Silva, Sara, Wang, Jun, Darzi, Youssef, Faust, Karoline, Kurilshikov, Alexander, Bonder, Marc Jan, Valles-Colomer, Mireia, Vandeputte, Doris, Tito, Raul Y., Chaffron, Samuel, Rymenans, Leen, Verspecht, Chloë, De Sutter, Lise, Lima-Mendez, Gipsi, D'hoe, Kevin, Jonckheere, Karl, Homola, Daniel, Garcia, Roberto, Tigchelaar, Ettje F., Eeckhaudt, Linda, Fu, Jingyuan, Henckaerts, Liesbet, Zhernakova, Alexandra, Wijmenga, Cisca, and Raes, Jeroen

Published
2016

31. A Dual UHPLC-HRMS-Based Fecal Metabolomics and Lipidomics Analysis and Automated Data Processing Pipeline for Comprehensive Gut Phenotyping

Author

Vangeenderhuysen, Pablo, primary, Van Arnhem, Jasmien, additional, Pomian, Beata, additional, De Graeve, Marilyn, additional, De Commer, Lindsey, additional, Falony, Gwen, additional, Raes, Jeroen, additional, Zhernakova, Alexandra, additional, Fu, Jingyuan, additional, Hemeryck, Lieselot Y., additional, and Vanhaecke, Lynn, additional

Published
2023
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32. A Dual UHPLC-HRMS-Based Fecal Metabolomics and Lipidomics Analysis and Automated Data Processing Pipeline for Comprehen-sive Gut Phenotyping

Author

Vangeenderhuysen, Pablo, primary, Van Arnhem, Jasmien, additional, Pomian, Beata, additional, De Graeve, Marilyn, additional, De Commer, Lindsey, additional, Falony, Gwen, additional, Raes, Jeroen, additional, Zhernakova, Alexandra, additional, Fu, Jingyuan, additional, Hemeryck, Lieselot Y., additional, and Vanhaecke, Lynn, additional

Published
2023
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36. Variation and transmission of the human gut microbiota across multiple familial generations

Author

Valles-Colomer, Mireia, Bacigalupe, Rodrigo, Vieira-Silva, Sara, Suzuki, Shinya, Darzi, Youssef, Tito, Raul Y., Yamada, Takuji, Segata, Nicola, Raes, Jeroen, and Falony, Gwen

Subjects
Adult, Microbiology (medical), 16S, Adolescent, Immunology, DIVERSITY, CHILDREN, Bacterial Physiological Phenomena, Applied Microbiology and Biotechnology, Microbiology, Article, Cohort Studies, LIKELIHOOD, Feces, Young Adult, RICHNESS, RNA, Ribosomal, 16S, REGRESSION, 80 and over, Genetics, Humans, Family, R PACKAGE, Preschool, Child, Aged, LEVEL ANALYSIS, Ribosomal, Aged, 80 and over, RISK, Science & Technology, Bacteria, Cell Biology, Child, Preschool, Female, Gastrointestinal Microbiome, Metagenomics, Middle Aged, Metagenome, CATALOG, BODY-MASS INDEX, RNA, Microbiome, Life Sciences & Biomedicine
Abstract

Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother–daughter pairs, decreasing with increasing daughter’s age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation., Quantitative metagenomic analyses of gut microbiomes reveals kinship, together with current cohabitation, as drivers of microbial community transmission and persistence between family members over three to five generations.

Published
2021
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37. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamineN-oxide with implications for heart and kidney disorders

Author

Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia, Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe-Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael, Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Pedro Coelho, Luis, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Zucker, Jean-Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad, Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, Dumas, Marc-Emmanuel, Imperial College London, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitätsklinikum Leipzig, European Molecular Biology Laboratory [Heidelberg] (EMBL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Paris-Saclay Food and Bioproduct Engineering (SayFood), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Procédés biotechnologiques au service de l'environnement (UR PROSE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Charles Viollette (ICV) - ULR 7394 (ICV), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Institut Supérieur d'Agriculture-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

ObjectivesThe host-microbiota co-metabolite trimethylamineN-oxide (TMAO) is linked to increased thrombotic and cardiovascular risks. Here we, sought to i) characterize which host variables contribute to fasting serum TMAO levels in real-life settings ii) identify potential actionable therapeutic means related to circulating TMAO.DesignWe applied “explainable” machine learning, univariate-, multivariate- and mediation analyses of fasting plasma TMAO concentration and a multitude of bioclinical phenotypes in 1,741 adult Europeans of the MetaCardis study. We expanded and validated our epidemiological findings in mechanistic studies in human renal fibroblasts and a murine model of kidney fibrosis following TMAO exposure.ResultsNext to age, kidney function was the primary variable predicting circulating TMAO in MetaCardis, with microbiota composition and diet playing minor, albeit significant roles. Mediation analysis revealed a causal relationship between TMAO and kidney function decline that strengthened at more severe stages of cardiometabolic disease. We corroborated our findings in preclinical models where TMAO exposure augmented conversion of human renal fibroblasts into myofibroblasts and increased kidney scarringin vivo. Mechanistically, TMAO aggravated kidney fibrosis due to ERK1/2 hyperactivation synergistically with TGF-β1 signaling. Consistent with our findings, patients receiving next-generation glucose-lowering drugs with reno-protective properties, had significantly lower circulating TMAO when compared to propensity-score matched control individuals.ConclusionAfter age, kidney function is the major determinant of fasting circulating TMAO in adults. Our findings of lower TMAO levels in individuals medicated with reno-protective anti-diabetic drugs suggests a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk that merits urgent investigation in human trials.Data availability statementRaw shotgun sequencing data that support the findings of this study have been deposited in the European Nucleotide Archive with accession codes PRJEB37249, PRJEB38742, PRJEB41311 and PRJEB46098. Serum NMR and urine NMR metabolome data have been uploaded to Metabolights with accession number MTBLS3429; serum GC-MS and isotopically quantified serum metabolites (UPLC–MS/MS) are available from MassIVE with accession numbers MSV000088042 and MSV000088043, respectively.

Published
2022
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41. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults

Author

Hansen, Lea B. S., Roager, Henrik M., Søndertoft, Nadja B., Gøbel, Rikke J., Kristensen, Mette, Vallès-Colomer, Mireia, Vieira-Silva, Sara, Ibrügger, Sabine, Lind, Mads V., Mærkedahl, Rasmus B., Bahl, Martin I., Madsen, Mia L., Havelund, Jesper, Falony, Gwen, Tetens, Inge, Nielsen, Trine, Allin, Kristine H., Frandsen, Henrik L., Hartmann, Bolette, Holst, Jens Juul, Sparholt, Morten H., Holck, Jesper, Blennow, Andreas, Moll, Janne Marie, Meyer, Anne S., Hoppe, Camilla, Poulsen, Jørgen H., Carvalho, Vera, Sagnelli, Domenico, Dalgaard, Marlene D., Christensen, Anders F., Lydolph, Magnus Christian, Ross, Alastair B., Villas-Bôas, Silas, Brix, Susanne, Sicheritz-Pontén, Thomas, Buschard, Karsten, Linneberg, Allan, Rumessen, Jüri J., Ekstrøm, Claus T., Ritz, Christian, Kristiansen, Karsten, Nielsen, H. Bjørn, Vestergaard, Henrik, Færgeman, Nils J., Raes, Jeroen, Frøkiær, Hanne, Hansen, Torben, Lauritzen, Lotte, Gupta, Ramneek, Licht, Tine Rask, and Pedersen, Oluf

Published
2018
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42. Human gut microbes impact host serum metabolome and insulin sensitivity

Author

Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Nielsen, Henrik Bjorn, Hyotylainen, Tuulia, Nielsen, Trine, Jensen, Benjamin A.H., Forslund, Kristoffer, Hildebrand, Falk, Prifti, Edi, Falony, Gwen, Le Chatelier, Emmanuelle, Levenez, Florence, Dore, Joel, Mattila, Ismo, Plichta, Damian R., Poho, Paivi, Hellgren, Lars I., Arumugam, Manimozhiyan, Sunagawa, Shinichi, Vieira-Silva, Sara, Jorgensen, Torben, Holm, Jacob Bak, Trost, Kajetan, Kristiansen, Karsten, Brix, Susanne, Raes, Jeroen, Wang, Jun, Hansen, Torben, Bork, Peer, Brunak, Soren, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf

Subjects
Insulin resistance -- Genetic aspects, Amino acids, Metabolic diseases, Cardiovascular diseases, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched- chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders., Insulin resistance (IR) and metabolic syndrome are risk factors for both type 2 diabetes and ischaemic cardiovascular diseases, pathologies that are in epidemic growth worldwide. Mounting evidence suggests a link [...]

Published
2016
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44. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Author

Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifti, Edi, Aron-Wisnewsky, Judith, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouya, Chloé, André, Sébastien, Andreelli,, Fabrizio, Blüher, Matthias Blüher, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue, Holmes, Bridget, Ji, Boyang, Krogh Pedersen, Helle, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Mannerås-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B, Touch, Sothea, Vieira-Silva, Sara, Consortium, MetaCardis, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvol, Michael, Pedersen, Oluf Borbye, Bork, Peer, Dusko Ehrlich, Stanislav, Zucker, Jens-Daniel, Bäckhed, Fredrik, Raes, Jeroen, Clément, Karine, Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifti, Edi, Aron-Wisnewsky, Judith, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouya, Chloé, André, Sébastien, Andreelli,, Fabrizio, Blüher, Matthias Blüher, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue, Holmes, Bridget, Ji, Boyang, Krogh Pedersen, Helle, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Mannerås-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B, Touch, Sothea, Vieira-Silva, Sara, Consortium, MetaCardis, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvol, Michael, Pedersen, Oluf Borbye, Bork, Peer, Dusko Ehrlich, Stanislav, Zucker, Jens-Daniel, Bäckhed, Fredrik, Raes, Jeroen, and Clément, Karine

Abstract

Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.

Published
2022

45. Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice

Author

UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service d'endocrinologie et de nutrition, Le Roy, Tiphaine, Moens De Hase, Emilie, Van Hul, Matthias, Paquot, Adrien, Pelicaen, Rudy, Régnier, Marion, Depommier, Clara, Druart, Céline, Everard, Amandine, Maiter, Dominique, Delzenne, Nathalie M., Bindels, Laure B., de Barsy, Marie, Loumaye, Audrey, Hermans, Michel, Thissen, Jean-Paul, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, Muccioli, Giulio, Cani, Patrice D., UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service d'endocrinologie et de nutrition, Le Roy, Tiphaine, Moens De Hase, Emilie, Van Hul, Matthias, Paquot, Adrien, Pelicaen, Rudy, Régnier, Marion, Depommier, Clara, Druart, Céline, Everard, Amandine, Maiter, Dominique, Delzenne, Nathalie M., Bindels, Laure B., de Barsy, Marie, Loumaye, Audrey, Hermans, Michel, Thissen, Jean-Paul, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, Muccioli, Giulio, and Cani, Patrice D.

Abstract

Objective: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115T, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice. Design: We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115T on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice. Results: This newly identified bacterium was detected in 62.7%-69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115T, but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115T administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition. Conclusions: These results suggest that D. welbionis J115T directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.

Published
2022

46. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity:effect of biotin and prebiotic supplementation on improved metabolism

Author

Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, Clement, Karine, Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, and Clement, Karine

Published
2022

49. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

Author

Forslund, Kristoffer, Hildebrand, Falk, Nielsen, Trine, Falony, Gwen, Le Chatelier, Emmanuelle, Sunagawa, Shinichi, Prifti, Edi, Vieira-Silva, Sara, Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Arumugam, Manimozhiyan, Kristiansen, Karsten, Voigt, Anita Yvonne, Vestergaard, Henrik, Hercog, Rajna, Costea, Paul Igor, Kultima, Jens Roat, Li, Junhua, Jorgensen, Torben, Levenez, Florence, Dore, Joel, Nielsen, H. Bjorn, Brunak, Soren, Raes, Jeroen, Hansen, Torben, Wang, Jun, Ehrlich, S. Dusko, Bork, Peer, and Pedersen, Oluf

Subjects
Microbiota (Symbiotic organisms) -- Physiological aspects, Diabetes therapy -- Physiological aspects, Metformin -- Patient outcomes -- Physiological aspects, Type 2 diabetes -- Drug therapy -- Physiological aspects -- Patient outcomes, Environmental issues, Science and technology, Zoology and wildlife conservation, Drug therapy, Physiological aspects, Patient outcomes
Abstract

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported (1, 2). In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis (3, 4). Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa (3, 4). These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication., T2D is a disorder of elevated blood glucose levels (hyperglycaemia) primarily due to insulin resistance and inadequate insulin secretion, with rising global prevalence. Genetic and environmental risk factors are known, [...]

Published
2015

50. 440: STANDARDIZED FECAL MICROBIOTA TRANSPLANTATION THROUGH MICROBIOME-GUIDED DONOR SELECTION IN ACTIVE ULCERATIVE COLITIS PATIENTS: A RANDOMIZED, PLACEBO-CONTROLLED INTERVENTION STUDY

Author

Deleu, Sara, primary, Caenepeel, Clara, additional, Arnauts, Kaline, additional, Castellanos, Jorge Francisco Vazquez, additional, Braekeleire, Sara, additional, Machiels, Kathleen, additional, Baert, Filip J., additional, Mana, Fazia, additional, Pouillon, Lieven, additional, Hindryckx, Pieter, additional, Lobaton, Triana, additional, Louis, Edouard, additional, Franchimont, Denis, additional, Ferrante, Marc, additional, Sabino, João, additional, Vieira-Silva, Sara, additional, Falony, Gwen, additional, Raes, Jeroen, additional, and Vermeire, Severine, additional

Published
2022
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